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D‐4F, an apolipoprotein A‐1 mimetic, inhibit endothelium‐derived microparticles‐induced endothelial nitric oxide synthase dysfunction
Author(s) -
Ou Jingsong,
Densmore John C,
Kaul Sushma,
Guice Karen S,
Pritchard Kirkwood A,
Oldham Keith T
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a290-a
Subject(s) - enos , umbilical vein , endothelial dysfunction , endothelium , nitric oxide , superoxide , endothelial stem cell , nitric oxide synthase type iii , nitric oxide synthase , medicine , endocrinology , vasodilation , chemistry , biochemistry , in vitro , enzyme
Endothelium‐derived microparticles (EMP) have recently been identified in patients with cardiovascular diseases and are suggested as markers of endothelial dysfunction. D‐4F, an apolipoprotein A‐1 mimetic, has been reported to improve endothelium‐ and endothelial nitric oxide synthase (eNOS) dependent vasodilation in a variety of vascular diseases. However, whether D‐4F can preserve eNOS function in EMP‐treated endothelial cells remains unknown. Bovine aortic endothelial cells (BAEC) were pretreated with EMP (2x10 6 /ml) derived from plasminogen activated inhibitor‐1 stimulated human umbilical vein endothelial cells for 30 min. Superoxide anion (O 2 ·– ) and nitric oxide (NO) generation were determined. EMP significantly increased O 2 ·– generation where L‐nitroargininemethylester partially inhibit it, and decreased NO generation. Western blots show EMP decreased phosphorylation of eNOS with unaltered eNOS expression. However, when BAEC were pretreated with EMP + D‐4F 10 μg/ml, D‐4F partially restored phosphorylation of eNOS. Our findings indicate D‐4F can restore in part, eNOS function in EMP‐treated endothelial cell cultures and may provide a new therapeutic approach for treating endothelial dysfunction.